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The underlying disease process of ALS (also known as Lou Gehrig's disease), a fatal neurodegenerative disease that paralyzes its victims, has long eluded scientists and prevented development of effective therapies.
That changed in August 2011, when Foundation researcher Dr. Teepu Siddique and his team published a paper identifying a faulty protein pathway as a common cause of all forms of ALS. This was the first time a common cause of all forms had been discovered. In November 2011, Dr. Siddique and his team released another paper which identified a second faulty gene in this same pathway.
The resources on this page explain these discoveries and discuss their impact for patients and families worldwide. Please take a moment to view the short video below, read more about the discovery, and browse a selection of comments from experts, media, patients and families.
The basis of ALS is a broken down protein "recycling system" in the neurons of the spinal cord and the brain. A protein, ubiquilin2, has the critical job of recycling damaged or misfolded proteins in motor and cortical neurons, shuttling them off to be reprocessed.
In people with ALS, ubiquilin2 isn't doing its job. As a result, the damaged proteins and ubiquilin2 accumulate in the motor neurons in the spinal cord and brain. The protein accumulations resemble twisted skeins of yarn—characteristic of ALS—and cause the degeneration of the neurons. The cell can't repair or maintain itself and becomes severely damaged. This breakdown occurs in all three forms of ALS: hereditary, which is called familial; ALS that is not hereditary, called sporadic; and ALS that targets the brain, ALS/dementia. In a follow-up paper, Dr. Siddique and his team reported on another faulty gene, a new "loafing worker" called sequestosome1, in the same recycling pathway.
"This opens up a whole new field for finding an effective treatment for ALS," said senior author Teepu Siddique, M.D., the Les Turner ALS Foundation/Herbert C. Wenske Professor of the Davee Department of Neurology and Clinical Neurosciences at Northwestern's Feinberg School and a neurologist at Northwestern Memorial Hospital. "We can now test for drugs that would regulate this protein pathway or optimize it, so it functions as it should in a normal state." In addition, the discovery of the second gene "gives us a clear target to develop drug therapies [and] strengthens our belief that this broken system is at the heart of ALS."
The breakthrough discovery of ubiquilin2 is detailed in a paper published in Nature. The discovery of sequestosome1 is detailed in a paper published in the Archives of Neurology. You can read a stories from Northwestern University Feinberg School of Medicine on the discovery of ubiquilin2 and sequestosome1. You may also view the short video above, which discusses the vital importance of the discovery of ubiquilin2.
This lab, which was first established in 1979 with a staff of four, has now grown to become an international center of research excellence. Due to cuts in NIH funding, Dr. Siddique is depending on private donors to keep the momentum of his research moving forward. Please give today.
"When researchers earlier this week reported the discovery of a common mechanism—a cause, if you will—behind the various forms of the fatal neurological disorder known as Lou Gehrig’s disease, the announcement held special meaning for one group of everyday Chicagoans who have been dedicated to such a breakthrough for more than three decades."
- Chicago Sun-Times, "Local group has worked hard for breakthrough in Lou Gehrig’s disease"
“The discovery provides an opening to finding treatments for ALS and could also pay dividends by showing the way to treatments for other, more common neurodegenerative diseases such as Alzheimer's, dementia and Parkinson's.”
- Chicago Tribune, "Cause of ALS is found, Northwestern team says"
"Siddique has been searching for the causes and underlying mechanism of ALS for more than a quarter century. He said he was initially drawn to it because, 'It was one of the most difficult problems in neurology and the most devastating, a disease without any treatment or known cause.'"
- Northwestern University, "Major ALS Breakthrough"
From the Journal
Archives of Neurology, "SQSTM1 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis"
(Both articles are preview only; subscription required for full-text access.)
ABC7 Chicago, "Study finds pathway to ALS cure"
Chicago Sun-Times, "Northwestern researchers report breakthrough in ALS research"
Fox 32 News, "Northwestern University Finds Common Cause of ALS"
Fox News, "Scientists Discover Cause of All Types of ALS"
U.S. News and World Report, "Researchers Say They've Found Common Cause of All Types of ALS"
USA Today, "Researchers say they’ve found a common cause of ALS"
Yahoo News via HealthDay, "Researchers Say They've Found Common Cause of All Types of ALS"
HealthNews, "Researchers Pinpoint Cause of ALS"
International Business Times, "Cause of Lou Gehrig's Disease Identified, Could ALS Cure be Next?"
Medical News Today, "Common Cause Of All ALS Forms Identified - Seen As A Major ALS Breakthrough"
Medscape, "Common Cause of ALS Discovered"
Boston Herald, "Breakthrough could lead to effective treatment for ALS"
New York Times, "Possible Culprit Is Found for Lou Gehrig’s Disease"
San Francisco Chronicle, "Cause of ALS is Found, Brings Hope for a Cure for Alzheimer's Disease"
St. Petersburg Times, "Scientists cite gains on Lou Gehrig's disease"
BBC News, "Cell recycling system 'damaged in nerve disease'"
The Globe and Mail, "ALS finding may lead to future treatment"
Press TV, "Key to fatal nerve disease discovered"
Sydney Morning Herald, "Cause found for deadly disease"
The Times of India, "Cause of fatal paralytic disease discovered"
UK Press Association, "Protein 'key to motor neurone help'"
Vancouver Sun, "Common cause found for all forms of ALS"
The Chamernik Family
"Instead of thinking maybe there will be a treatment to manage the disease for my children's grandchildren, now I think it could be just a matter of years...it gives me a little bit of hope that I didn't have before."
- Aimee Chamernik
The Pagan Family
"I was amazed...I only try to teach them [my children], 'Live life to the fullest. Every day, treasure life because you don't know what it can bring you.'"
- Ana Pagan
Fox 32 News, "Northwestern University Finds Common Cause of ALS"
The Heronemus Family
"Today that hope has form.
Today that hope has transformed our walk into a march, for
Today, like every day, is the day the Lord has made.
Today, like every day, we will rejoice and be glad."
- Steve Heronemus